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Am. J. Respir. Crit. Care Med., Volume 156, Number 4, October 1997, S82-S88

Genetics of Native Airway Responsiveness in Mice

GEORGE T. DE SANCTIS and JEFFREY M. DRAZEN

Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

The inbred mouse represents a powerful tool for dissecting both simple and complex traits. Genetic studies in the mouse should identify disease genes acting in the same biochemical pathway as in the human. Problems associated with genetic heterogeneity, inability to control environmental conditions, lack of an abundant supply of genetic markers, and ethical considerations regarding human genetic crosses are but some of the reasons to study airway responsiveness in the mouse. At present, only a handful of studies have shed light on the genetics of airway responsiveness; even fewer have sought to identify genetic loci that regulate this trait. It is clear that both genetic and environmental factors influence the asthma phenotype and that genetic background is an important consideration when interpreting segregation analysis data. The controversy over the specific mode of inheritance and number and location of quantitative trait loci (QTL) illustrates the need for additional studies. However, given that numerous candidate loci implicated in the pathogenesis of asthma map near QTLs identified in two recent studies, and given the considerable homology between the human and mouse genome, a targeted search for susceptibility genes is warranted in the human. Ideally, these regions will demonstrate linkage in humans. Thus, further work remains to be done to create detailed maps of the regions of linkage in the mouse, and to ultimately identify gene(s) that modify airway responsiveness. De Sanctis GT, Drazen JM. Genetics of native airway responsiveness in mice.




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